The cardiac relaxing system (CRS: sarcoplasmic reticulum) represents at least one of the potential pools of calcium available for activation of contraction. Considerable data have been accumulated regarding the kinetics of calcium binding by CRS and its possible relation to relaxation. The process by which calcium might be released from CRS is less well studied. We propose to study calcium accumulation and release and factors that control them, i.e. the relation of calcium release to calcium binding and factors which control them independently. The proposed areas of study will include: 1) further characterization of the normal kinetics using stopped flow spectrophotometry and analysis of binding sites, 2) the use of pathologic and pharmacologic interventions and specific inhibitors, 3) indirect methods for measuring protein conformation, and (4) attempts to isolate and purify calcium binding proteins. The information gained from these studies will be used to evaluate the importance of this membrane system with regard to drug actions and control of cardiac contractility.